JP2007505933A5 - - Google Patents
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- JP2007505933A5 JP2007505933A5 JP2006527162A JP2006527162A JP2007505933A5 JP 2007505933 A5 JP2007505933 A5 JP 2007505933A5 JP 2006527162 A JP2006527162 A JP 2006527162A JP 2006527162 A JP2006527162 A JP 2006527162A JP 2007505933 A5 JP2007505933 A5 JP 2007505933A5
- Authority
- JP
- Japan
- Prior art keywords
- aryl
- heteroaryl
- lower alkyl
- group
- substituents
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 125000000217 alkyl group Chemical group 0.000 claims 151
- 125000003118 aryl group Chemical group 0.000 claims 132
- 125000001072 heteroaryl group Chemical group 0.000 claims 114
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims 105
- 125000001424 substituent group Chemical group 0.000 claims 92
- 229910052739 hydrogen Inorganic materials 0.000 claims 77
- 239000001257 hydrogen Substances 0.000 claims 77
- 229910052736 halogen Inorganic materials 0.000 claims 68
- 150000002367 halogens Chemical class 0.000 claims 64
- 125000002723 alicyclic group Chemical group 0.000 claims 53
- 125000003342 alkenyl group Chemical group 0.000 claims 53
- 150000002431 hydrogen Chemical class 0.000 claims 52
- 125000000304 alkynyl group Chemical group 0.000 claims 51
- 125000000623 heterocyclic group Chemical group 0.000 claims 49
- 229940002612 prodrug Drugs 0.000 claims 47
- 239000000651 prodrug Substances 0.000 claims 47
- 150000003839 salts Chemical class 0.000 claims 47
- 125000006413 ring segment Chemical group 0.000 claims 43
- 125000004093 cyano group Chemical group *C#N 0.000 claims 38
- 150000002148 esters Chemical class 0.000 claims 38
- 239000012453 solvate Substances 0.000 claims 38
- 229910052757 nitrogen Inorganic materials 0.000 claims 34
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims 33
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 25
- 150000001875 compounds Chemical class 0.000 claims 25
- 125000005842 heteroatom Chemical group 0.000 claims 25
- 229910052760 oxygen Inorganic materials 0.000 claims 25
- 229910052717 sulfur Inorganic materials 0.000 claims 25
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims 22
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims 22
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims 22
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims 22
- 125000002619 bicyclic group Chemical group 0.000 claims 19
- 125000004076 pyridyl group Chemical group 0.000 claims 19
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 18
- 201000010099 disease Diseases 0.000 claims 15
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 claims 15
- 125000003710 aryl alkyl group Chemical group 0.000 claims 14
- -1 lower perhaloalkyl Chemical group 0.000 claims 13
- 239000003814 drug Substances 0.000 claims 12
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 claims 11
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims 11
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims 11
- 229910019142 PO4 Inorganic materials 0.000 claims 11
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims 11
- 125000003282 alkyl amino group Chemical group 0.000 claims 11
- 239000004202 carbamide Substances 0.000 claims 11
- DMSZORWOGDLWGN-UHFFFAOYSA-N ctk1a3526 Chemical compound NP(N)(N)=O DMSZORWOGDLWGN-UHFFFAOYSA-N 0.000 claims 11
- 125000004663 dialkyl amino group Chemical group 0.000 claims 11
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims 11
- AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 claims 11
- 125000002541 furyl group Chemical group 0.000 claims 11
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims 11
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims 11
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims 11
- 125000002950 monocyclic group Chemical group 0.000 claims 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 11
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims 11
- 239000010452 phosphate Substances 0.000 claims 11
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 11
- 229940124530 sulfonamide Drugs 0.000 claims 11
- 150000003456 sulfonamides Chemical class 0.000 claims 11
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims 11
- 150000003457 sulfones Chemical class 0.000 claims 11
- 229930192474 thiophene Natural products 0.000 claims 11
- 206010028980 Neoplasm Diseases 0.000 claims 9
- 125000001246 bromo group Chemical group Br* 0.000 claims 9
- 125000001309 chloro group Chemical group Cl* 0.000 claims 9
- 101710113864 Heat shock protein 90 Proteins 0.000 claims 8
- 102100034051 Heat shock protein HSP 90-alpha Human genes 0.000 claims 8
- 125000004122 cyclic group Chemical group 0.000 claims 7
- 206010016654 Fibrosis Diseases 0.000 claims 6
- 229940034982 antineoplastic agent Drugs 0.000 claims 6
- 239000002246 antineoplastic agent Substances 0.000 claims 6
- 125000004429 atom Chemical group 0.000 claims 6
- 230000001404 mediated effect Effects 0.000 claims 6
- 239000003795 chemical substances by application Substances 0.000 claims 5
- 229940079593 drug Drugs 0.000 claims 5
- 229940124597 therapeutic agent Drugs 0.000 claims 5
- 229930194542 Keto Natural products 0.000 claims 4
- ZSWFCLXCOIISFI-UHFFFAOYSA-N cyclopentadiene Chemical compound C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 claims 4
- 125000005843 halogen group Chemical group 0.000 claims 4
- 125000000468 ketone group Chemical group 0.000 claims 4
- 239000008194 pharmaceutical composition Substances 0.000 claims 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims 4
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims 4
- 208000023275 Autoimmune disease Diseases 0.000 claims 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 3
- 201000009030 Carcinoma Diseases 0.000 claims 3
- 208000035473 Communicable disease Diseases 0.000 claims 3
- 102000004190 Enzymes Human genes 0.000 claims 3
- 108090000790 Enzymes Proteins 0.000 claims 3
- 208000029523 Interstitial Lung disease Diseases 0.000 claims 3
- 208000012902 Nervous system disease Diseases 0.000 claims 3
- 208000025966 Neurological disease Diseases 0.000 claims 3
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical group OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 claims 3
- 206010039710 Scleroderma Diseases 0.000 claims 3
- 208000019802 Sexually transmitted disease Diseases 0.000 claims 3
- 208000006011 Stroke Diseases 0.000 claims 3
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims 3
- 239000004037 angiogenesis inhibitor Substances 0.000 claims 3
- 230000003388 anti-hormonal effect Effects 0.000 claims 3
- 230000000340 anti-metabolite Effects 0.000 claims 3
- 230000000118 anti-neoplastic effect Effects 0.000 claims 3
- 229940100197 antimetabolite Drugs 0.000 claims 3
- 239000002256 antimetabolite Substances 0.000 claims 3
- 125000005160 aryl oxy alkyl group Chemical group 0.000 claims 3
- 201000011510 cancer Diseases 0.000 claims 3
- 229910052799 carbon Inorganic materials 0.000 claims 3
- 230000007882 cirrhosis Effects 0.000 claims 3
- 208000019425 cirrhosis of liver Diseases 0.000 claims 3
- 229940127089 cytotoxic agent Drugs 0.000 claims 3
- 239000002254 cytotoxic agent Substances 0.000 claims 3
- 231100000599 cytotoxic agent Toxicity 0.000 claims 3
- 239000003534 dna topoisomerase inhibitor Substances 0.000 claims 3
- 229940088598 enzyme Drugs 0.000 claims 3
- 230000004761 fibrosis Effects 0.000 claims 3
- 230000003176 fibrotic effect Effects 0.000 claims 3
- 239000003966 growth inhibitor Substances 0.000 claims 3
- 208000019622 heart disease Diseases 0.000 claims 3
- 230000003054 hormonal effect Effects 0.000 claims 3
- 208000027866 inflammatory disease Diseases 0.000 claims 3
- 201000006334 interstitial nephritis Diseases 0.000 claims 3
- 208000028867 ischemia Diseases 0.000 claims 3
- 208000011379 keloid formation Diseases 0.000 claims 3
- 208000032839 leukemia Diseases 0.000 claims 3
- 230000003211 malignant effect Effects 0.000 claims 3
- 230000004060 metabolic process Effects 0.000 claims 3
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 claims 3
- 229960001156 mitoxantrone Drugs 0.000 claims 3
- 229910052697 platinum Inorganic materials 0.000 claims 3
- 208000005987 polymyositis Diseases 0.000 claims 3
- CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 claims 3
- 229960000624 procarbazine Drugs 0.000 claims 3
- 230000002062 proliferating effect Effects 0.000 claims 3
- 206010039073 rheumatoid arthritis Diseases 0.000 claims 3
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims 3
- 230000001225 therapeutic effect Effects 0.000 claims 3
- 229940044693 topoisomerase inhibitor Drugs 0.000 claims 3
- 238000011282 treatment Methods 0.000 claims 3
- 125000003545 alkoxy group Chemical group 0.000 claims 2
- 125000004104 aryloxy group Chemical group 0.000 claims 2
- 230000008512 biological response Effects 0.000 claims 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 2
- 239000003607 modifier Substances 0.000 claims 2
- 125000002524 organometallic group Chemical group 0.000 claims 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims 2
- 150000003235 pyrrolidines Chemical class 0.000 claims 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims 1
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 claims 1
- 102100039064 Interleukin-3 Human genes 0.000 claims 1
- 108010002386 Interleukin-3 Proteins 0.000 claims 1
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 claims 1
- 125000004414 alkyl thio group Chemical group 0.000 claims 1
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 claims 1
- 150000001720 carbohydrates Chemical class 0.000 claims 1
- 230000008878 coupling Effects 0.000 claims 1
- 238000010168 coupling process Methods 0.000 claims 1
- 238000005859 coupling reaction Methods 0.000 claims 1
- 239000003102 growth factor Substances 0.000 claims 1
- 230000003394 haemopoietic effect Effects 0.000 claims 1
- 125000004438 haloalkoxy group Chemical group 0.000 claims 1
- 239000000367 immunologic factor Substances 0.000 claims 1
- 238000000338 in vitro Methods 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 150000003009 phosphonic acids Chemical class 0.000 claims 1
- 238000011321 prophylaxis Methods 0.000 claims 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims 1
- 0 *C[n]1c(O*)nc2c1c(*)c(*)nc2* Chemical compound *C[n]1c(O*)nc2c1c(*)c(*)nc2* 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US50413503P | 2003-09-18 | 2003-09-18 | |
| US59146704P | 2004-07-26 | 2004-07-26 | |
| PCT/US2004/031248 WO2005028434A2 (en) | 2003-09-18 | 2004-09-20 | Novel heterocyclic compounds as hsp90-inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2007505933A JP2007505933A (ja) | 2007-03-15 |
| JP2007505933A5 true JP2007505933A5 (enExample) | 2007-11-08 |
Family
ID=34381103
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2006527162A Ceased JP2007505933A (ja) | 2003-09-18 | 2004-09-20 | Hsp90インヒビターとしての新規なヘテロ環化合物 |
Country Status (14)
| Country | Link |
|---|---|
| US (8) | US7138401B2 (enExample) |
| EP (2) | EP2145888A1 (enExample) |
| JP (1) | JP2007505933A (enExample) |
| KR (1) | KR20060070572A (enExample) |
| CN (1) | CN101906106A (enExample) |
| AU (2) | AU2004274507B2 (enExample) |
| BR (1) | BRPI0414533A (enExample) |
| CA (1) | CA2539548A1 (enExample) |
| EA (1) | EA010160B1 (enExample) |
| IL (1) | IL174375A0 (enExample) |
| MX (1) | MXPA06002997A (enExample) |
| NO (1) | NO20061396L (enExample) |
| NZ (1) | NZ546611A (enExample) |
| WO (1) | WO2005028434A2 (enExample) |
Families Citing this family (190)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
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| US8741578B2 (en) * | 2004-11-02 | 2014-06-03 | The Regents Of The University Of California | Methods of detecting chronic lymphocytic leukemia with Hsp90 and ZAP-70 |
| EP1814392A4 (en) * | 2004-11-02 | 2008-06-11 | Conforma Therapeutics Corp | METHODS AND COMPOSITIONS FOR TREATING CHRONIC LYMPHOCYTIC LEUKEMIA |
| US8212012B2 (en) * | 2004-11-03 | 2012-07-03 | University Of Kansas | Novobiocin analogues having modified sugar moieties |
| US9120774B2 (en) | 2004-11-03 | 2015-09-01 | University Of Kansas | Novobiocin analogues having modified sugar moieties |
| BRPI0609509A2 (pt) * | 2005-03-30 | 2010-04-13 | Conforma Therapeutics Corp | composto ou um polimorfo, solvato, tautÈmero, enanciÈmero, pró-droga ou sal farmaceuticamente aceitável do mesmo, composição farmacêutica, e, uso do composto, polimorfo, solvato, tautÈmero, enanciÈmero, pró-droga ou sal farmaceuticamente aceitável |
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| WO2007024680A1 (en) | 2005-08-22 | 2007-03-01 | Amgen Inc. | Pyrazolopyridine and pyrazolopyrimidine compounds useful as kinase enzymes modulators |
| ES2577514T3 (es) | 2005-08-22 | 2016-07-15 | The Regents Of The University Of California | Antagonistas de TLR |
| US20070049608A1 (en) * | 2005-08-24 | 2007-03-01 | Fink Cynthia A | Pyrrolopyridine, pyrrolopyrimidine and pyrazolopyridine compounds, compositions comprising them, and methods of their use |
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| WO2007058852A2 (en) * | 2005-11-10 | 2007-05-24 | Smithkline Beecham Corporation | Inhibitors of akt activity |
| JP2009515884A (ja) * | 2005-11-10 | 2009-04-16 | スミスクライン・ビーチャム・コーポレイション | Akt活性の阻害剤 |
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| US20070253896A1 (en) * | 2006-02-07 | 2007-11-01 | Conforma Therapeutics Corporation | 7,9-Dihydro-Purin-8-One and Related Analogs as HSP90-Inhibitors |
| WO2007097839A2 (en) * | 2006-02-16 | 2007-08-30 | Massachusetts Eye And Ear Infirmary | Ansamycin analogs or heat shock 90 inhibitors in combination with pdt treatin conditions of the eye |
| NZ572600A (en) * | 2006-05-12 | 2011-08-26 | Myrexis Inc | 6-Amino-purine derivatives for the treatment of cancer and fibrogenetic disorders |
| WO2007142755A2 (en) * | 2006-05-31 | 2007-12-13 | The Regents Of The University Of California | Purine analogs |
| DK2034839T3 (en) | 2006-06-30 | 2017-12-04 | Sloan-Kettering Institute For Cancer Res | TREATMENT OF NEURODEGENERATIVE DISEASES BY INHIBITION OF HSP90 |
| US20080009508A1 (en) * | 2006-07-10 | 2008-01-10 | Lucie Szucova | 6,9-Disubstituted Purine Derivatives And Their Use For Treating Skin |
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| LT5623B (lt) | 2008-04-30 | 2010-01-25 | Biotechnologijos Institutas, , | 5-aril-4-(5-pakeistieji 2,4-dihidroksifenil)-1,2,3-tiadiazolai kaip hsp90 šaperono slopikliai ir tarpiniai junginiai jiems gauti |
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2004
- 2004-09-20 EP EP09157018A patent/EP2145888A1/en not_active Withdrawn
- 2004-09-20 KR KR1020067007478A patent/KR20060070572A/ko not_active Ceased
- 2004-09-20 EA EA200600594A patent/EA010160B1/ru not_active IP Right Cessation
- 2004-09-20 US US10/946,645 patent/US7138401B2/en not_active Expired - Lifetime
- 2004-09-20 US US10/946,628 patent/US7129244B2/en not_active Expired - Lifetime
- 2004-09-20 CN CN2010101575972A patent/CN101906106A/zh active Pending
- 2004-09-20 CA CA002539548A patent/CA2539548A1/en not_active Abandoned
- 2004-09-20 EP EP04788954A patent/EP1670802A4/en not_active Withdrawn
- 2004-09-20 AU AU2004274507A patent/AU2004274507B2/en not_active Ceased
- 2004-09-20 US US10/946,637 patent/US7148228B2/en not_active Expired - Lifetime
- 2004-09-20 US US10/945,851 patent/US7138402B2/en not_active Expired - Lifetime
- 2004-09-20 WO PCT/US2004/031248 patent/WO2005028434A2/en not_active Ceased
- 2004-09-20 JP JP2006527162A patent/JP2007505933A/ja not_active Ceased
- 2004-09-20 NZ NZ546611A patent/NZ546611A/en not_active IP Right Cessation
- 2004-09-20 BR BRPI0414533-0A patent/BRPI0414533A/pt not_active IP Right Cessation
- 2004-09-20 MX MXPA06002997A patent/MXPA06002997A/es active IP Right Grant
-
2006
- 2006-03-16 IL IL174375A patent/IL174375A0/en unknown
- 2006-03-27 NO NO20061396A patent/NO20061396L/no not_active Application Discontinuation
- 2006-09-12 US US11/531,218 patent/US20070173483A1/en not_active Abandoned
- 2006-09-12 US US11/531,221 patent/US20070185064A1/en not_active Abandoned
- 2006-09-29 US US11/537,002 patent/US20070111996A1/en not_active Abandoned
- 2006-09-29 US US11/537,017 patent/US20070111997A1/en not_active Abandoned
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2010
- 2010-06-30 AU AU2010202750A patent/AU2010202750B2/en not_active Ceased
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